The role of mast cells in the pathogenesis of pain in chronic pancreatitis.

The role of mast cells in the pathogenesis of pain in chronic pancreatitis.
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DOI:
10.1186/1471-230x-5-8
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发表时间:
2005-03-03
影响因子:
2.4
通讯作者:
Pasricha PJ
Pasricha PJ
中科院分区:
医学4区
文献类型:
--
作者:
Hoogerwerf WA;Gondesen K;Xiao SY;Winston JH;Willis WD;Pasricha PJ

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慢性胰腺炎疼痛的生物学基础还知之甚少。在其他情况下,肥大细胞也与疼痛的发病机制有关。我们假设肥大细胞在慢性胰腺炎的疼痛中起作用。我们在慢性胰腺炎患者的尸检标本中检测了疼痛与肥大细胞的关系。我们使用三硝基苯磺酸(TNBS)诱导的野生型(WT)和肥大细胞缺陷小鼠(MCDM)慢性胰腺炎的实验模型进一步验证了我们的假设。对组织学诊断为慢性胰腺炎的档案组织进行鉴定,并对临床记录进行回顾,以确定是否存在人类报告的疼痛。计数肥大细胞数。使用von Frey细丝(VFF)来测量患有和不患有慢性胰腺炎的WT和MCDM小鼠的腹部撤退反应,以评估疼痛的存在。与无痛性慢性胰腺炎患者相比,患有疼痛的慢性胰腺炎患者的胰腺肥大细胞数量增加了3.5倍。与MCDM相比,患有慢性胰腺炎的WT小鼠在腹部VFF疼痛测试中明显更敏感。与无痛性慢性胰腺炎患者相比,有痛性慢性胰腺炎患者的胰腺肥大细胞数量更多。与WT相比,MCDM对慢性胰腺炎诱导后腹部的机械刺激不那么敏感。肥大细胞可能在慢性胰腺炎疼痛的发病机制中起重要作用。
The biological basis of pain in chronic pancreatitis is poorly understood. Mast cells have been implicated in the pathogenesis of pain in other conditions. We hypothesized that mast cells play a role in the pain of chronic pancreatitis. We examined the association of pain with mast cells in autopsy specimens of patients with painful chronic pancreatitis. We explored our hypothesis further using an experimental model of trinitrobenzene sulfonic acid (TNBS) -induced chronic pancreatitis in both wild type (WT) and mast cell deficient mice (MCDM). Archival tissues with histological diagnoses of chronic pancreatitis were identified and clinical records reviewed for presence or absence of reported pain in humans. Mast cells were counted. The presence of pain was assessed using von Frey Filaments (VFF) to measure abdominal withdrawal responses in both WT and MCDM mice with and without chronic pancreatitis. Humans with painful chronic pancreatitis demonstrated a 3.5-fold increase in pancreatic mast cells as compared with those with painless chronic pancreatitis. WT mice with chronic pancreatitis were significantly more sensitive as assessed by VFF pain testing of the abdomen when compared with MCDM. Humans with painful chronic pancreatitis have an increased number of pancreatic mast cells as compared with those with painless chronic pancreatitis. MCDM are less sensitive to mechanical stimulation of the abdomen after induction of chronic pancreatitis as compared with WT. Mast cells may play an important role in the pathogenesis of pain in chronic pancreatitis.